This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This research will use EELS to image iodinated small molecules bound to Alzheimer[unreadable]s related beta-amyloid fibrils. Several iodinated small molecules have recently been identified by a proprietary biochemical assay to bind with high affinity to amyloid fibrils. In order to evaluate the potential utility of radiolabeled versions of these compounds as in vivo contrast agents for Alzheimer[unreadable]s plaques by e.g., SPECT, this research seeks to develop an in vitro imaging method to more rapidly assess which non-radiolabeled versions of these molecules have the characteristics of: 1) high affinity, 2) high density, and 3) high selectivity for labeling amyloid fibrils. If successful, this research will result in a non radioactivity-based method to visually confirm the capability of small molecules to specifically label amyloid deposits in tissues, which should dramatically expedite the discovery and development of new diagnostic agents for Alzheimer[unreadable]s disease.